1. Investigation of the effect of maternal iodine status on cognitive outcomes in the offspring Sarah Bath Professor Margaret Rayman University of Surrey Professor Jean Golding Colin Steer Dr Pauline Emmett University of Bristol

2. Overview Iodine Essential component of T4 and T3 Growth, development and metabolism Brain and neurological development

3. Why iodine is important Reduced I.Q. 1 Cretinism 1 Reduced mental and motor skills 3 Impaired psychomotor skills 2 ADHD 4 Increased infant mortality 1 1. Delange 1994; 2. Pop 1999; 3. Pop 2004; 4. Vermiglio 2004

4.  Pregnancy is the life stage with the highest requirement for iodine  Adult requirement: 150 µg/day (WHO)  Pregnancy requirement: 250 µg/day (WHO) Zimmermann 2009, Endocr Rev 30, 376-408 Iodine requirements

5. Use of a biomarker for assessment of iodine status  Iodine status is determined from urinary iodine concentration  90% of iodine ingested is assumed to be excreted  For an individual, 24-hr urinary iodine excretion is the best measure  For a population, a spot-urine sample is used  Urinary creatinine measured to correct for urine volume

6. Iodine Deficiency in the UK - Historical  Iodine deficiency used to be widespread in Britain with high rate of goitre and even of cretinism in some areas  Goitre was still present in many areas until the 1960s Areas of endemic goitre in the past Phillips D 1997; Lee S et al. 1994 Patient with Derbyshire neck

7. How goitre was eradicated in the UK Iodine concentration of milk increased Milk consumption increased Three-fold increase in iodine intakes between 1950s and 1980s

8.  Urinary iodine excretion measured in 737 adolescent girls (14-15 yrs)  Nine centres across the UK  Iodine excretion indicated mild deficiency in the cohort  Concern that iodine deficiency may be widespread in the UK Current iodine status * Percentage of schoolgirls Urinary iodine excretion (μg/L) mild def. moderate def. severe def. *Vanderpump et al. Lancet 2011

9. 0 50 100 150 200 250 Median Urinary I Conc (µg/L) Adequate range for population median iodine concentration in pregnancy 2 Whole Group Iodine supplement users Non iodine supplement users ** p<0.001 ** Iodine status of Surrey pregnant women 1 1. Bath et al. Proc Nutr Soc 2010; 2. Andersson et al. 2007

10. Does iodine deficiency in the UK matter? Aims:  Evaluate impact of maternal iodine deficiency on cognition in offspring in a region of mild-moderate iodine deficiency

11. Our current study investigated 1000 ALSPAC women The women were selected on the basis of:  availability of a urine sample at 12 weeks gestation and  their children having a measure of intelligence quotient (IQ) at age eight years Methods: Participants

12. Methods: Outcome measures Sub-optimal performance = bottom 25% of scores Intelligence Quotient (IQ) Weschler Intelligence Scale for Children III UK (WISC-III UK ) at age 8 years Reading ability Neale Analysis of Reading Ability at age 9 years School performance Key Stage 2 at age 11 years

13. Results: Iodine status  This cohort of pregnant women were classified as mildly- to-moderately iodine deficient 1,2  Median urinary iodine concentration = 91.8 µg/L  Median iodine:creatinine ratio = 123 µg/g  61.6% of the women were iodine deficient (< 150 µg/g) when using creatinine-adjusted values  None of the women took iodine-containing supplements or seaweed during pregnancy 1. Andersson et al. Public Health Nutr 2007; 10: 1606-1611; 2. Zimmermann. Thyroid 2007; 17: 829-835.

14. No. of children OR 95% CI P value measured IQ (age 8) Verbal 9511.360.99, 1.86 0.06 Performance 9511.591.17, 2.16 0.003 Total score 9511.551.06, 2.28 0.020 Reading (age 9) Accuracy 8491.891.24, 2.87 0.003 Comprehension 8511.451.05, 2.01 0.020 School attainment (age 11) English 8651.290.94, 1.78 0.12 Maths 8691.601.15, 2.22 0.006 Science 8691.401.02, 1.92 0.039 Results: Cognitive outcomes Risk of being in the bottom quartile of scores if maternal iodine status was deficient rather than sufficient (unadjusted)

15. Adjusted* risk of being in the bottom quartile of scores if maternal iodine status was deficient rather than sufficient No. of children OR 95% CI P value measured IQ (age 8) Performance 792 1.461.02, 2.10 0.038 Total score 7921.551.06, 2.28 0.025 Reading (age 9) Accuracy 7131.891.24, 2.87 0.003 School attainment (age 11) Maths 7251.671.09, 2.56 0.02 Science 7261.400.94, 2.08 0.10 Results: Cognitive outcomes adjusted for confounders Confounders: gender, preterm birth, birth weight, ethnicity, breastfeeding, maternal age, smoking, alcohol use, parity, stressful life events, parenting score, maternal depression, n-3 fatty acid and iron intake, fish oil supplements, maternal and paternal education, housing status, crowding, family adversity and HOME score

16. Results: Effect of degree of iodine deficiency IQ ScoreReading Accuracy

17.  Iodine status in UK pregnant women of the ALSPAC cohort is mildly-to-moderately deficient  This level of deficiency appears sufficient to affect brain development in the offspring as shown by: Significantly lower total IQ at age 8 Significantly lower reading accuracy at age 9 Poorer school performance at age 11, which is significantly poorer in mathematics  The adverse effects on brain development increase with a higher level of iodine deficiency Conclusions from our ALSPAC data

18. Sponsors Acknowledgements Collaborators ALSPAC Executive Prof Jean Golding Colin Steer Dr Pauline Emmett Dr John Wright Analysts Dr Christine Sieniawska Dr Andrew Taylor Mr Alan Walter Dr Alex Richardson